On December 29, 2016, the U.S. Food and Drug Administration (“FDA”) surprised many in the radiopharmacy industry by issuing a long-awaited draft guidance entitled “Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies.” The guidance addresses conditions under which the FDA does not intend to take action for violations of 505, 502(f)(1) and 501(a)(2)(B) of the Food, Drug and Cosmetic Act (“FD&C Act”) when a 503A state-licensed nuclear pharmacy that is not a 503B outsourcing facility compounds or repackages radiopharmaceuticals for human use. Although the guidance will need some tweaking and it fails to acknowledge ongoing distribution problems in the radiopharmacy supply chain, it is a very welcome development given that the most recent official Agency guidance on this topic was issued in 1984.
Yes – 1984. For this reason alone, please join us and many others across the country as we ring in the New Year with a toast to FDA. Cheers!
As a threshold issue, the guidance acknowledges that although radiopharmaceuticals are generally not eligible for the 503A exemptions, there are certain circumstances under which the FDA will not take action for violations of the FD&C Act. Specifically, the guidance sets forth two major categories of these circumstances: (1) “minor deviations” and repackaging; and (2) compounding other than minor deviations.
With regard to the first category, the guidance defines “minor deviation” as a change from the approved labeling in radioactivity, volume and/or the step-by-step procedures when compounding the radiopharmaceutical from an FDA-approved drug product in a patient-ready dose, e.g. the addition of a supplemental amount of radioactive material so that a radiopharmaceutical can be provided to a geographically distant patient. The guidance defines “repackaging” as the act of placing an FDA-approved radiopharmaceutical into a new container, without reconstituting, diluting, mixing or combining the product with another ingredient. With regard to compounding, that constitutes “minor deviation” and repackaging, the guidance states that the FDA will not take action for violations of the FD&C Act where the radiopharmaceutical is compounded or repackaged from: (1) an FDA-approved drug product; (2) by or under the direct supervision of a licensed, authorized nuclear pharmacist; (3) in compliance with relevant USP chapter; and (4) in accordance with all applicable requirements of the Nuclear Regulatory Commission (“NRC”). Further the compounded or repackaged radiopharmaceutical must be distributed only in states in which the compounded or repackaged radiopharmaceutical meets all applicable state requirements, and must not be transferred or sold by an entity other than the entity that completed the compounding or repackaging.
With regard to the second category concerning compounding other than “minor deviations,” the conditions largely mirror the conditions of eligibility for that of the 503A exemptions, and also include many of the above procedural conditions concerning minor deviation compounding and repackaging. In addition to these conditions, the guidance sets forth conditions that are specific to non-minor deviation compounding. Specifically, the FDA states that a compounded radiopharmaceutical must: (1) not appear on a list of drug products that have been withdrawn or removed from the market; (2) not be identified on a list of drugs or categories of drugs that present demonstrable difficulties for compounding that are reasonably likely to lead to an adverse effect on the safety or effectiveness of the drug; and (3) not be essentially a copy of a marketed FDA-approved radiopharmaceutical. To this last condition, the FDA provides additional guidance on when a compounded drug is considered “essentially a copy of a marketed FDA-approved radiopharmaceutical.”
Finally, the guidance clarifies that, although drug manufacturers are generally required to register annually with the FDA pursuant to Section 510(b)(1) of the FD&C Act, pharmacies that compound or repackage radiopharmaceuticals may qualify for an exemption from registration. Additionally, the guidance states that with respect to entities that do not qualify for these exemptions, the FDA does not intend to take action for failure to register and list radiopharmaceuticals that are compounded or repackaged in accordance with the guidance.
Stir the eggnog and lift the hot toddy – Happy New Year, everybody!